Anti-HTLV antibody profiling reveals an antibody signature for HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP).
BACKGROUND
HTLV-I is the causal agent of adult T cell leukemia (ATLL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Biomarkers are needed to diagnose and/or predict patients who are at risk for HAM/TSP or ATLL. Therefore, we investigated using luciferase immunoprecipitation technology (LIPS) antibody responses to seven HTLV-I proteins in non-infected controls, asymptomatic HTLV-I-carriers, ATLL and HAM/TSP sera samples. Antibody profiles were correlated with viral load and examined in longitudinal samples.


RESULTS
Anti-GAG antibody titers detected by LIPS differentiated HTLV-infected subjects from uninfected controls with 100% sensitivity and 100% specificity, but did not differ between HTLV-I infected subgroups. However, anti-Env antibody titers were over 4-fold higher in HAM/TSP compared to both asymptomatic HTLV-I (P < 0.0001) and ATLL patients (P < 0.0005). Anti-Env antibody titers above 100,000 LU had 75% positive predictive value and 79% negative predictive value for identifying the HAM/TSP sub-type. Anti-Tax antibody titers were also higher (P < 0.0005) in the HAM/TSP compared to the asymptomatic HTLV-I carriers. Proviral load correlated with anti-Env antibodies in asymptomatic carriers (R = 0.76), but not in HAM/TSP.


CONCLUSIONS
These studies indicate that anti-HTLV-I antibody responses detected by LIPS are useful for diagnosis and suggest that elevated anti-Env antibodies are a common feature found in HAM/TSP patients.
Burbelo
Peter D
PD
Neurobiology and Pain Therapeutics Section, Laboratory of Sensory Biology, National Institute of Dental and Craniofacial Research, Bethesda, MD 20892, USA. burbelop@nidcr.nih.gov
Meoli
Elise
E
Leahy
Hannah P
HP
Graham
Jhanelle
J
Yao
Karen
K
Oh
Unsong
U
Janik
John E
JE
Mahieux
Renaud
R
Kashanchi
Fatah
F
Iadarola
Michael J
MJ
Jacobson
Steven
S
D002353:Carrier State; D005260:Female; D015481:HTLV-I Antibodies / Q000097:blood*; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000175:diagnosis / Q000276:immunology* / Q000821:virology; D013118:Spinal Cord Diseases / Q000175:diagnosis / Q000276:immunology* / Q000821:virology; D019562:Viral Load; D014764:Viral Proteins / Q000276:immunology
D015481:HTLV-I Antibodies; D014764:Viral Proteins